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2012 Grants - Decourt

Preclinical Testing of Lenalidomide as Anti-Amyloid Treatment for Alzheimer's Disease

Boris Decourt, Ph.D.
Banner Research Institute
Phoenix, Arizona

2012 New Investigator Research Grant

Tumor necrosis factor-alpha (TNF-alpha) is a hormone-like molecule that tends to proliferate in the brains of people with Alzheimer's disease. This molecule may help promote the inflammation that occurs during the early stages of the disease. Recent studies have found that high doses of the drug thalidomide can reduce brain levels of TNF-alpha in mice engineered to develop Alzheimer's-like symptoms. Thalidomide also appears to reduce brain levels of the protein fragment beta-amyloid, a key suspect in dementia. However, because high doses of thalidomide can cause severe side effects in humans, the treatment's use in clinical trials is unfeasible.

Boris Decourt, Ph.D., and colleagues have identified a drug that may be just as effective as thalidomide at combating TNG-alpha, but without the severe side effects. This drug is called lenalidomide, and it has already been approved by the U.S. Food and Drug Administration to fight cancer. For their proposed study, the researchers plan to test lenalidomide's ability to reduce TNG-alpha and beta-amyloid levels in Alzheimer's-like mice. The team will also assess whether their treatment can reduce brain inflammation and ameliorate certain aspects of cognitive decline, including reduced spatial learning and memory. Results of this study could refine our understanding of the role that TGN-alpha plays in Alzheimer's. They could also lead to clinical trials that test the effectiveness of lenalidomide as a novel dementia therapy for people.